Recent investigations of colorectal cancer (CRC) have suggested that the accumulation of specific alterations in cell-growth regulating genes trigger the stage-wise progression to malignancy and that at least some of them could be useful for prognosis. In this study, the frequency, location and type of mutations of the Ki-ras proto-oncogene exons 1-2 and p53 tumour-suppressor gene exons 5-9 were analysed in colorectal carcinomas of 72 patients from the European Saar-Luxembourg region using PCR-SSCP screening and direct sequencing. The incidences of Ki-ras activating and p53 inactivating point mutations in these European samples were much lower (Ki-ras: 5 (6.9%) and p53: 13 (18.1%)) than reported for both genes in American studies (40-50% at least) (P < 1 x 10(-3)). These results suggest that other genetic mechanisms than those proposed for the classic adenoma-carcinoma sequence model can frequently underlie CRC development and that Ki-ras and p53 mutations should not be considered as universal markers for CRC.